Apparatus for mechanical processing of a sample and a member of such an apparatus

ABSTRACT

An apparatus for facilitating the release of an ingredient of a plastic or elastic sample of a pharmaceutical or confectionery material while the sample is in contact with a liquid medium which includes a base, a fixed lower jaw, a movable upper jaw and a member for moving the upper jaw toward and away from the lower jaw, a support for mounting and supporting a sample in the space between the upper surface of the lower jaw and the lower surface of the upper jaw, and a container surrounding both the jaws and sample so as to confine a liquid medium to the area surrounding the sample.

The present invention relates to a method and an apparatus formechanical processing of a plastic or elastic sample and to a member ofsuch an apparatus.

BACKGROUND

For studying the properties of a plastic or elastic sample whensubjected to mechanical processing, an apparatus is needed which makesit possible to carry out reproducible tests.

Present-day techniques comprise e.g. a masticating device as disclosedby Kleber et al. in Journal of Dental Research, 60 (1981):2, pp 109-114,which is used for in vitro assessment of the abrasive effects of chewinggum on teeth, and a measuring device as described by Christrup et al. inArch. Pharm. Chem. Sci., 1986, 14, pp 30-36, which is used for in vitromeasurements of the release of substances included in a chewing gum.

The prior art devices comprise two mutually reciprocatory jaws orpistons which are disposed in a container and between which the sampleis to be processed.

The properties which may be of interest to determine thus are, interalia, the action exerted by the sample on the pistons or some partthereof, the plasticity of the sample and/or the release of substancesincluded in the sample to a liquid surrounding it, all as a function ofthe processing time and/or the processing technique. The purpose of thedetermination may be comparative, i.e. primarily for quality control,and/or imitative, e.g. with respect to in vivo processing by chewing.

A particularly interesting field for using such a mechanical processingapparatus is the processing of pharmaceutical preparations in the formof plastic samples, preferably chewing gums, in which case it should bepossible in a reproducible manner to determine the period of time duringwhich active substances in the sample are released to a liquidsurrounding the sample.

In addition to the processing technique, the release of substances maybe affected by the components included in the chewing gum, such asconsistency agents, softeners, preservatives, gum bases, flavourings, aswell as active substances in the form of drugs or nicotine, but also bythe method of making the chewing gum. Further, the release is affectedby the environment in which it takes place, i.e. the temperature and thecomposition of the liquid surrounding the sample, and the apparatusshould be able to maintain at least the temperature constant.

One drawback of the prior art devices is the problem of cleaning thecontainer or reservoir in which the sample is processed. The tendency ofthe sample to move or spread outside the processing area of the pistonsor jaws has also been observed in the prior art devices. Another problemconcerns the fact that the sample tends to adhere sometimes to one jaw,sometimes to the other and, above all, to separate parts floating freelyin the liquid and escaping further processing.

In view of these problems, it is therefore very difficult to obtain anexact and reproducible processing of the samples by using the prior artdevices. From this of course follows that it will not be possible toobtain reliable and reproducible release rates which can be used forscientific or manufacturing purposes.

THE PRESENT INVENTION

The most important object of the present invention thus is to provide anapparatus and a method for mechanical processing of a pharmaceutical orconfectionery sample in a reproducible manner.

To sum up, the present invention concerns an apparatus for mechanicalprocessing of a pharmaceutical or confectionery plastic or elasticsample for the release of substances from the sample into a surroundingliquid medium. The apparatus includes a substantially vertical containerreleasably mounted on a base. The apparatus also comprises a first jawfor receiving the sample. This jaw is fixed to the base and arranged inthe lower end of the container. Means for sealing the lower end of thecontainer against leakage of the liquid are also provided. A second jawfacing the first jaw is vertically movable and rotatable for subjectingthe sample to compression and shearing forces. The apparatus alsoincludes means for driving the second jaw.

Preferably, the apparatus also includes means for controlling thetemperature of the liquid medium.

According to the invention, it has also been found that in cases where ahigh degree of accuracy and reproducibility is required, a separatereinforcing member which may be in the form of a flat and/or disc-shapeddevice or member should be processed at the same time as the sample. Byusing this disc-shaped device or reinforcing member the sample will holdtogether and can be prevented from splitting up into several pieces orfrom otherwise moving outside the processing area between the jaws.

To permit a substantially free movement within the material of thesample during processing, the disc-shaped member suitably isforaminated. This also increases the adherence between the member andthe sample, making it more vigorous than the adherence between thesample and the jaws.

The disc-shaped member may advantageously be a net or a perforated discand consist of plastic, e.g. nylon or any other material which is inertto the components in the sample and to the liquid in which the sample isprocessed.

It is furthermore preferred that the container is double-walled and madeof a transparent material, such as glass or plastic. The flexibility ofthe apparatus is further increased if the distance between the jaws canbe adjusted and, to this end, the upper jaw is preferably mounted insuch a way that it is vertically adjustable.

The surfaces of the jaws facing each other suitably are frictionsurfaces, i.e. exhibit a relatively large friction with respect to thesample. A particularly suitable feature is however using smooth frictionsurfaces, in which case the necessary friction may optionally beachieved by blasting. Completely smooth surfaces may however also beused. In such case, the jaws will be very easy to clean, which is ofimportance to prevent a sample from contaminating the following sampleand so forth.

In order to ensure stirring of the liquid in the container duringprocessing, at least one jaw suitably forms a gap with the inner wall ofthe container.

The movement of the upper jaw may be purely reciprocating, but in orderto imitate in vivo processing of a chewing gum, the apparatus maypreferably have means for rotating the jaws relative to each other whenin their turning positions closest to each other.

The invention also comprises a method for mechanical processing of aplastic or elastic pharmaceutical or confectionery sample for therelease of substances from the sample into a surrounding liquid medium,comprising immersing a reinforcing member in the medium, immersing thesample in the medium, and subjecting the sample and the memberessentially simultaneously to repeated compression and shearing forces.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the invention will now be described in moredetail hereinbelow with reference to the accompanying drawing in which:

FIG. 1 is a longitudinal section of an apparatus according to theinvention, and

FIG. 2 is a top plan view of a device according to the invention.

FIG. 3 is a diagram showing release of nicotine versus time.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The embodiment shown in FIG. 1 of an apparatus according to theinvention comprises a cylindrical, double-walled container 1. A base 2consists of a base plate 3, a spacer plate 4 and a sealing plate 5 whichare held together by a stud bolt 6 on which a fixed jaw 7 can also bescrewed. A spacer sleeve 8 encloses the jaw 7 and is removably mountedand non-rotatably connected to the jaw 7 by means of a stop screw 9.

The lower open end of the container 1 can be passed over the sleeve 8with liquid-tight fit with respect thereto. A collar 10 with a flange 11is glued to the lower end of the container 1. An O-ring 12 is mounted inmating grooves in the flange 11 and the sealing plate 5 which arepressed against each other by means of a clamping member 13.

A second jaw 15 is removably mounted on a reciprocatory piston 14, suchthat the jaw 15 is located above the jaw 7. The jaw 15 can bereciprocated relative to the jaw 7 by drive means (indicated at 16) andhas adjustable stroke length, stroke velocity and stroke frequency. Thedrive means 16 can also be arranged to rotate the jaw 15 relative to thejaw 7, especially when the jaw 15 is in its turning position closest tothe jaw 7.

In FIG. 1, there is also shown a sample 17 which partly encloses adisc-shaped member 18 according to the invention. The disc-shaped member18 more specifically is in the form of a net, as shown in more detail inFIG. 2, and is circular, having a slightly smaller diameter than theinner diameter of the container 1, for instance 1 mm less. The net 18has a higher adhesive capacity with respect to the sample 17 than thejaws 7, 15.

Instead of a net, the disc-shaped member 18 may consist of any otherforaminated member, for instance a perforated disc. The member 18 shouldbe substantially two-dimensional, i.e. have but a small extent in thedirection of movement of the jaw 15. Alternatively, the member 18 couldhowever also be a spacer element determining the minimum distancebetween the jaws 7 and 15, i.e. the lower end position of the jaw 15.

Since the container 1 is double-walled, it can be used forthermostatting a liquid contained therein, such as water or artificialsaliva. The container may consist of glass, plastic or other suitablematerial that does not react with the liquid used or any of thecomponents in the sample 17.

The surfaces 19, 20 of the jaws 7, 15 facing each other are frictionsurfaces which may be formed with grooves, notches or otherirregularities to retain the sample 17 when it is subjected to pressureand rotation by the jaws 7, 15. However, the required friction can alsobe achieved by means of smooth surfaces, which of course makes it easierto clean the jaws 7, 15 between different processing operations.

It is desirable to have a gap between the jaw 15 and the inner wall ofthe container 1. The size of this gap is suitably determined empiricallyon the basis of e.g. the desired stroke frequency, the volume of thesample and the liquid volume to be displaced. Since it is oftendesirable to have liquid solutions with as high a concentration aspossible of substances released from the sample during the processing,the liquid volume in the container should be relatively small and thusalso said gap.

For analysing substances released from the sample 17, the apparatus maycomprise different types of probes for measuring pH and temperature, andfor automatic measurements of the composition of the liquid etc.

To determine e.g. the release of different substances in a sample 17,the apparatus described above can be used in the following way. Thesample 17 and the member 18 are placed on the jaw 7, whereupon asuitable liquid is supplied to and thermostatted in the container 1. Thejaw 15 is thereafter set in motion according to a predetermined movementpattern, and sampling from the liquid container 1 is performed atpreselected points of time, whereupon the sample or liquid phase isanalysed with respect to the substance or substances the release ofwhich should be measured.

During processing, the plastic sample 17 will be flattened and partlyenclose the member 18 thus performing a reinforcing function and holdingthe sample 17 together. If, nevertheless, parts of the sample 17 shouldbe torn loose from the side thereof located below the member 18, thiswill prevent the separated parts from moving upwards into the liquid. Inthis way, the separated parts can again be easily integrated with thesample reinforced by the member 18. Since the spacer sleeve 8 extendshigher than the jaw 7, the member 18 tends to lift the sample 17 off thejaw 7 between each stroke of the jaw 15.

EXAMPLES

The invention is further illustrated by the following Examples

EXAMPLE 1

Samples of NICORETTE chewing gum were weighed.

The casing of a double-walled container in an apparatus according to theinvention was filled with water to be circulated and having atemperature of 37° C. An aqueous solution containing 0.1% artificialsaliva was heated to 37° C. and poured in the container. A sample ofNICORETTE was immersed into the aqueous medium in the container andplaced on the jaw. The upper jaw was actuated to move to a depressedposition for fixing the sample. After about 5 min, temperatureequilibrium between medium and sample had been reached, and the upperjaw was actuated to move up and down, executing a rotary movement whenin its lowest turning position in order to repeatedly subject the sampleto compression and shearing forces.

EXAMPLE 2

Example 1 was repeated, however with a disc-shaped net immersed into themedium in the container together with the NICORETTE sample. Volumes of0.5 ml of the medium were withdrawn from the container afterrespectively 2, 5, 10, 20, 30 and 45 min, and the amount of nicotine ineach volume was analysed by standard methods. The results (mean valuesof 6 samples) are given in the diagram of FIG. 3.

It is evident to a person skilled in the art that several differentmodifications of the embodiments described above are possible within thescope of the invention, such as it is defined in the accompanyingclaims.

I claim:
 1. An apparatus for facilitating the release of an ingredientof a plastic or elastic sample of a pharmaceutical or confectionerymaterial while the sample is in contact with a liquid medium, saidapparatus comprising the combination of(a) a base (2), (b) a first jaw(7) fixed on said base (2) and having an upper surface (19) againstwhich a sample positioned immediately thereabove can be compressed, (c)a second jaw (15) positioned above said first jaw and having a lowersurface against which said sample positioned immediately therebelow canbe compressed, (d) support means (8) for supporting a sample at a pointwhich is intermediate the upper surface of said first jaw (7) and thelower surface of said second jaw (15), said support means including aseparate member (18) that is foraminated so that a sample will extendabove, below and through the separate member (18), (e) means (14, 16)for moving said second jaw (15) toward and away from said first jaw (7)and which is capable of imparting a rotary movement to said second jawwhen said jaw is in its lowest position so that said jaws willrepetitively knead a sample placed therebetween; and (f) a verticalcontainer (1) extending upwardly from said base (2) and closelysurrounding said first and second jaws (7, 15) so as to confine a liquidmedium to the area surrounding said sample.
 2. Apparatus according toclaim 1 wherein said container (1) is a cylinder.
 3. Apparatus accordingto claim 2 wherein the cylinder (1) is double-walled and made of atransparent material.
 4. Apparatus according to claim 3 wherein saidtransparent material is glass.
 5. An apparatus according to claim 1wherein said separate member (18) is a net which is inert to the sampleand to the liquid medium.